ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1627419
This article is part of the Research TopicCommunity Series in Immune Responses Against Tumors - From the Bench to the Bedside: Volume IIView all 9 articles
CXCR7-TAGLN2 Protein Complex Regulates Invasion and Metastasis in Papillary Thyroid Carcinoma: A Potential Therapeutic Target
Provisionally accepted
- Department of General Surgery, First Hospital of Lanzhou University, Lanzhou, China
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Objective To investigate the expression and clinical significance of CXCR7 and TAGLN2 in papillary thyroid carcinoma (PTC), and to explore the molecular mechanisms underlying the interaction between CXCR7 and TAGLN2 in regulating PTC invasion and metastasis. Methods Paraffin-embedded tissue sections were obtained from 64 patients with PTC and 24 patients with nodular goiter who underwent surgical resection at The First Hospital of Lanzhou University between January 2017 and August 2020. Immunohistochemistry (IHC) was performed to assess protein expression levels of CXCR7 and TAGLN2. The associations between their expression and clinicopathological characteristics of PTC, as well as the correlation between CXCR7 and TAGLN2 expression levels, were analyzed. Human PTC cell lines were cultured in vitro, and co-immunoprecipitation (Co-IP) and immunofluorescence colocalization assays were conducted to evaluate the intracellular interaction between CXCR7 and TAGLN2. Lentiviral cotransfection techniques were employed to investigate the role of CXCR7 in modulating PTC cell invasion and metastasis via TAGLN2. Western blot analysis was performed to assess the levels of phosphorylated Smad2 (p-Smad2) and total Smad2. Results IHC results demonstrated that CXCR7 and TAGLN2 expression levels were significantly elevated in PTC tissues compared to benign thyroid tissues. High expression of both proteins was significantly associated with lymph node metastasis in PTC patients, and a significant positive correlation was observed between CXCR7 and TAGLN2 expression levels. In TPC-1 and BCPAP cells, CXCR7 and TAGLN2 exhibited similar subcellular localization and physically interacted. Silencing TAGLN2 markedly reduced TPC-1 and BCPAP cell migration, while concomitant overexpression of CXCR7 reversed this inhibitory effect. Mechanistically, Western blot analysis revealed that TAGLN2 knockdown led to a substantial decrease in p-Smad2 levels, confirming TAGLN2's contribution to TGF-β signaling activation. Furthermore, re-introducing CXCR7 into TAGLN2-silenced cells restored p-Smad2 levels, demonstrating that CXCR7 actively promotes TGF-β/Smad2 signaling. Conclusion CXCR7 and TAGLN2 are overexpressed in PTC and correlate closely with lymph node metastasis. CXCR7 may regulate PTC cell migration and invasion through interaction with TAGLN2, primarily by activating the TGF-β/Smad2 signaling pathway. The CXCR7-TAGLN2 protein complex represents a potential novel therapeutic target for PTC.
Keywords: Papillary thyroid carcinoma, CXCR7, Tagln2, metastasis, TGF-β signaling
Received: 13 May 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Zeng, Wang, Huang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Heng'Wei Zhang, ldyy_zhanghw@lzu.edu.cn
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